We have evaluated a number of compounds that influence the growth of lung cancer cells. We have reported previously on the autocrine role of gastrin release peptide, insulin-like growth factor, and transferrin--all of which stimulate growth for certain types of lung cancer. We have also shown that regulatory molecules such as glucagon and 13-cis-retinoic acid can inhibit the growth of a number of lung cancer cells lines. This experience has allowed us to focus on the signal transduction pathways most central to the process of cellular proliferation. In collaboration with Dr. M. Jett, we have recently presented data suggesting that 5-HETE, a product of 5- lipoxygenase activation may be a key intermediary in growth factor mediated growth stimulation of cancer cells. Since considerable information exists about the lipoxygenase pathway, we can potentially exploit the availability of existence of specific antagonists for application as biointervention tools. Systematic evaluation of the growth factor biology of early cancer cells may yield additional clues for the development of rational cancer intervention agents. Promising leads from in vitro models demonstrating significant anti-cancer effects with lung cancer cell lines will be followed up with evaluation of efficiency for in vivo model systems. The most interesting in vitro leads will be evaluated for clinical application in Phase I and II studies conducted by the BPRB. An important part of that effort would be the identification of markers for intermediate end points analysis; these would accelerate the process of determining the benefit of this class of intervention tools.